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About 4C

The Cardiovascular Comorbidity in Children with Chronic Kidney Disease Study

Adult patients with chronic kidney disease (CKD) are at markedly increased risk of dying from cardiovascular events. The risk is most dramatically increased in young patients with end-stage renal disease, who are almost as likely to die from cardiovascular causes as elderly individuals in the general population.

Early morphological and functional vascular abnormalities can be detected even in adolescents with CKD, but information about the prevalence, severity and natural course of vascular lesions in different stages of renal failure is lacking and the factors predisposing to an early onset and rapid progression of cardio-vascular morbidity are still elusive.

The pediatric population appears uniquely suited to study the effects of CKD on the cardiovascular system due to the virtual absence of vascular morbidity related to ageing, diabetes and smoking.

In order to improve our understanding of the causes and consequences of cardiovascular comorbidity in children with progressive CKD, a consortium of pediatric nephrologists in Europe has joined to perform a long-term prospective observational study following the cardiovascular health of children as they advance through successive stages of CKD.

The 4C Study is following 704 patients aged 6 to 17 years with a glomerular filtration rate of 10 to 60 ml/min/1.73 m² in 55 pediatric nephrology units in 14 European countries.

The morphology and function of the heart and the large arteries is regularly assessed by sensitive, non-invasive methods and the findings compared to a large group of healthy children.

Multiple potential clinical, anthropometric, biochemical and pharmacological risk factors are monitored prospectively and will be related to the cardiovascular status of the patients.

A whole genome association study will be performed to identify genetic variants associated with the progression of cardiovascular alterations and renal failure.

Patients are followed on when they enter end-stage renal disease. The effects of different replacement modalities (hemodialysis, peritoneal dialysis, transplantation with and without preceding dialysis) on cardiovascular health will be addressed in separate sub-studies (4C-D, 4C-T).

Effects of juvenile uremia on arterial and peritoneal histopathology, gene and protein expression will be investigated by biopsy sub-studies (4C-A, 4C-P).

To date, 737 patients in 55 participating centers from 12 European countries have been enrolled in the trial.

The study has been made possible by generous grants of the KfH Foundation for Preventive Medicine, the ERA-EDTA and the Integrated Research and Treatment Center Hannover.

The Cardiovascular Comorbidity in Children with Chronic Kidney Disease Study